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One-time CRISPR therapy keeps cholesterol lower for a full year in early trial

One-time CRISPR therapy keeps cholesterol lower for a full year in early trial

New Capabilities

Phase 1b data show a single infusion cut triglycerides 63% in patients with severely high levels

2 days ago: Phase 1b data show 63% triglyceride cut at Day 30

Overview

Updated 2 days ago

CRISPR Therapeutics' CTX310 cut triglycerides by 63% and ANGPTL3 by 65% a month after one infusion in 10 patients with severely high triglycerides, the company reported Nov. 9 at the American Heart Association meeting. The Phase 1b results follow a Phase 1a trial in which the same one-time treatment kept LDL cholesterol about 52% lower for a year.

The new group had a median baseline triglyceride level above 1,000 mg/dL, and all 10 patients had diabetes. No treatment-related serious adverse events or liver enzyme rises were reported; seven patients had at least 90 days of follow-up. CRISPR Therapeutics said additional Phase 1b cohorts are ongoing, and the FDA recently granted CTX310 Regenerative Medicine Advanced Therapy designations for severe hypertriglyceridemia and elevated LDL cholesterol.

Why it matters

A one-time infusion that permanently lowers lipids could replace daily pills for people who cannot control cholesterol or triglycerides.

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Key Indicators

52.5%
LDL cholesterol reduction at 12 months
Mean reduction from baseline at the highest dose in the Phase 1a trial.
47.8%
Triglyceride reduction at 12 months
Mean reduction from baseline at the highest dose in the Phase 1a trial.
79%
ANGPTL3 protein reduction at 12 months
Mean reduction at the highest dose, with a maximum of 89%.
15
Patients in Phase 1a trial
All completed at least one year of follow-up.
63%
Triglyceride reduction at Day 30 in Phase 1b
Mean reduction in 10 patients with severe hypertriglyceridemia after a single infusion.
65%
ANGPTL3 reduction at Day 30 in Phase 1b
Mean reduction in the same 10-patient severe hypertriglyceridemia cohort.
10
Patients in Phase 1b severe hypertriglyceridemia cohort
All had at least 30 days of follow-up as of the data cutoff.
15 years
Planned safety follow-up
FDA-recommended long-term monitoring for gene-editing therapy recipients.

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People Involved

LM
Luke Laffin, M.D.
Cleveland Clinic cardiologist and first author of the CTX310 trial
Leading the CTX310 clinical program at Cleveland Clinic
SM
Steven Nissen, M.D.
Cleveland Clinic cardiologist and senior investigator on the CTX310 trial
Senior investigator on the CTX310 program
AM
Ashish Sarraju, M.D.
Cleveland Clinic cardiologist and presenter of the Phase 1b CTX310 data
Presented Phase 1b CTX310 results at AHA Scientific Sessions 2026

Organizations Involved

CRISPR Therapeutics
CRISPR Therapeutics
Biotechnology company
Reported Phase 1b CTX310 data on Nov. 9; additional Phase 1b cohorts ongoing

The company developing CTX310, an in vivo CRISPR-Cas9 therapy targeting ANGPTL3.
Cleveland Clinic
Cleveland Clinic
Academic medical center
Presented Phase 1b CTX310 data at AHA on Nov. 9; conducted the Phase 1a trial

The hospital system that ran the first-in-human trial of CTX310 and presented Phase 1b data at AHA 2026.

Timeline

November 2025 November 2026

7 events Latest: 2 days ago
Tap a bar to jump to that date

  1. Phase 1b data show 63% triglyceride cut at Day 30

    Latest Clinical Data

    In 10 patients with severe hypertriglyceridemia, a single infusion of CTX310 reduced ANGPTL3 by 65% and triglycerides by 63% at Day 30. No treatment-related serious adverse events were reported.

  2. Nature publishes preclinical ANGPTL3 base-editing study

    Research

    The paper reported durable ANGPTL3 inactivation and lipid lowering in nonhuman primates for up to three years after a single dose, using a base editor delivered by lipid nanoparticle. It describes a separate approach from CTX310's Cas9 editing.

  3. FDA grants RMAT designations to CTX310

    Regulatory

    The FDA granted Regenerative Medicine Advanced Therapy designations to CTX310 for severe hypertriglyceridemia and for elevated LDL cholesterol, CRISPR Therapeutics said.

  4. OHSU enrolls first West Coast participant in CTX310 trial

    Clinical Trial

    Oregon Health & Science University became the first West Coast site to enroll a participant in the 17-center trial. The participant was a 54-year-old woman with severely high LDL who receives weekly apheresis.

  5. Results reach wider public audience

    Media

    Human Progress publishes an alert on the yearlong cholesterol reduction results.

  6. One-year durability data presented at ESC Congress

    Clinical Data

    NEJM-published results show LDL down 52.5% and triglycerides down 47.8% at 12 months.

  7. Initial CTX310 data shows two-month lipid drops

    Clinical Data

    Early Phase 1a results show CTX310 lowers LDL and triglycerides at two months.

Scenarios

1

Phase 1b confirms fixed-dose results

Likely Resolves by End of 2026

Discussed by: CRISPR Therapeutics, which said it expects to share Phase 1b data in the second half of 2026

The Phase 1b trial tested a fixed flat dose equivalent to the most effective Phase 1a dose in 10 patients with severe hypertriglyceridemia. At Day 30, it produced mean reductions of 65% in ANGPTL3 and 63% in triglycerides, with no treatment-related serious adverse events.

2

CTX310 advances to a pivotal trial

Possible Resolves by End of 2027

Discussed by: Cleveland Clinic investigators, who say the therapy could eventually give patients a choice between daily pills and a one-time infusion

A larger Phase 2 or Phase 3 trial would be needed to support FDA approval. The open questions are whether the effect persists beyond one year and whether the safety profile holds in a broader, more diverse population than the 15-patient Phase 1a.

3

Extended follow-up reports a treatment-related serious adverse event

Unlikely Resolves by End of 2027

Discussed by: Safety monitors and regulators; the FDA has recommended 15 years of follow-up for all gene-editing therapies

The one-year data showed no treatment-related serious adverse events, but the follow-up window is long. One participant died six months after infusion from advanced cardiovascular disease at the lowest dose, and one had a transient liver enzyme elevation. Permanent ANGPTL3 editing could in principle have effects that take years to appear.

4

Phase 1b effect lasts a full year

Likely Resolves by Nov 9, 2027

Discussed by: CRISPR Therapeutics, which said reductions were maintained in patients followed for at least 90 days

The company has not reported one-year Phase 1b data. A durable result at 12 months would show the fixed-dose regimen works as long as the Phase 1a infusion did.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

2003-2015

PCSK9 discovery to drug approval (2003-2015)

In 2003, researchers found that people with loss-of-function mutations in the PCSK9 gene had very low LDL cholesterol and low rates of heart disease. That genetic insight led to injectable antibody drugs approved in 2015 that block PCSK9 and lower LDL by about 60%.

Then

The drugs became major sellers but require injections every two to four weeks for life.

Now

They validated using human genetics to find cholesterol targets, the same path that led to ANGPTL3.

Why this matters now

CTX310 uses the same genetics-first logic as PCSK9 inhibitors but aims to make the effect permanent with one infusion.

2017

ANGPTL3 human genetics validation (2017)

A 2017 New England Journal of Medicine study of nearly 60,000 people found that carriers of ANGPTL3 loss-of-function mutations had lower LDL, lower triglycerides, and 34% lower odds of coronary artery disease, with no apparent health downsides.

Then

The study made ANGPTL3 a validated drug target and prompted development of antibody and gene-silencing approaches.

Now

It provided the natural experiment that CTX310 aims to replicate permanently.

Why this matters now

CTX310 is an attempt to convert any patient into a lifelong ANGPTL3 loss-of-function carrier.

November 2022

Hemgenix approval (2022)

The FDA approved Hemgenix (etranacogene dezaparvovec) in 2022 as the first one-time gene therapy for hemophilia B, delivered as a single infusion that lets patients produce clotting factor themselves.

Then

The therapy freed patients from regular factor infusions, at a cost of millions per dose.

Now

It established the regulatory and manufacturing precedent for one-time in vivo gene therapies.

Why this matters now

CTX310 follows the same one-time in vivo model but targets a common condition affecting millions, not a rare disease affecting thousands.

Sources

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Cleveland Clinic Newsroom BioSpace New York Times CNN TIME Human Progress PharmaDeviceNews Medical Xpress CRISPR Therapeutics Medical Daily Neo Science Hub synbiointel.com CRBC News Cleveland Clinic Cardiac Consult OHSU News Nature GlobeNewswire Investing.com CRISPR Medicine News Cleveland Clinic Newsroom